Many identified cell-surface antigens and receptors are members of the immunoglobulin superfamily (“IgSF”). IgSF proteins are characterized by one or more disulfide-linked loops formed between a highly conserved and properly spaced pair of cysteine residues, which organizes two β sheets composed of seven or nine antiparallel β-strands. These loops, which are referred to as immunoglobulin-like domains, are classified as variable or constant immunoglobulin-type domains. The variable (or V-type domains) polynucleotiderally possess disulfide loops with cysteine residues spaced by 65–75 amino acids and thus accommodate nine antiparallel β-strands whereas the constant (or C-type) domains typically exhibit intercysteine distances of 35–55 residues, and thus accommodate only seven antiparallel β-strands. Although some IgSF members contain multiple domains of a single type (e.g., NCAM which has five C2-type domains), most members possess either a single immunoglobulin-type domain or a mixture of both V-type and C-type domains (Williams and Barclay, 1988 “The immunoglobulin superfamily—domains for cell surface recognition”, Annu Rev Immunol. 6:381–405).
IgSF proteins are known to function as antigen receptors, cytokine receptors, receptors for cell-surface molecules (e.g., other IgSF proteins, adhesion molecules), and as counter-receptors.